The objective of this research program is to develop an understanding of the structural, electronic, and mechanistic features of the hydroporphyrin-containing enzymes. These catalyze important steps in key metabolic processes including the inorganic carbon, nitrogen, and sulfur cycles and many of the main energy producing pathways of microorganisms. The program has two specific aims: (1) to determine the significant differences in the properties of the complexes of hydroporphyrins, porphyrins, and other tetrapyrroles and (2) to develop a reactivity model for the F430 dependent reductive cleavage of methyl coenzyme M reductase to methane. Synthetic, small molecule analogues of enzyme active sites and prosthetic groups will be used in these investigations. The first aim will be addressed by testing the hypotheses that porphyrin, hydroporphyrins, corrins, and other tetrapyrroles are distinguished by their flexibility and by the optimal hole size and range of hole sizes readily accessible in their complexes and that the substituent stereochemistry can modulate the properties of the macrocycle. The hypotheses will be tested by examining chemical processes that require changes in metal ion radius or deformation of the tetrapyrrole macrocycle. The effect of the saturation level and substituent stereochemistry of the macrocycle on axial ligation equilibria and the accessibility of large radius metal ions like Ni(I) and Cu(I) will be investigated. Out-of-plane flexibility will be probed by investigations of the effect of the macrocycle saturation level on the barrier to aryl ring rotation in N-substituted tetraarylhydroporphyrins and by correlations of the cobalt-alkyl bond dissociation energies of R-Co(P)L with the macrocycle, P, and the steric bulk of the trans ligand, L. The second aim will be achieved by exploring the reactions of NiI(OEiBC). Emphasis will be placed on determining the role of hydride species in the chemistry of NiI(OEiBC), examining the ability of nickel complexes to cleave thioethers like methyl coenzyme M, and the detection of alkyl-Ni and hydrido-Ni OEiBC complexes.